Genetic factors play a substantive role in the susceptibility to common diseases. Due to recent and rapid advancements in characterization of genetic variants and large-scale genotyping platforms, multiple genes and genetic variants have now been identified for common, complex diseases. The most efficient method for gene identification at present appears to be large-scale association-based studies, which integrate genetic and epidemiological principles. As the strategy for gene identification studies has shifted towards genetic association-based methods rather than traditional linkage analysis, epidemiological methods are increasingly being integrated into genetic investigations. Consequently, the disciplines of genetics and epidemiology, which historically have functioned separately, have been integrated into a discipline referred to as genetic epidemiology. In this chapter, we review methods for establishing the genetic burden of complex genetic disease, followed by methods for gene and/or genetic variant identification and when appropriate we highlight the epidemiological issues that guide these methods.